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The authors report a study carried out on 82 patients affected with gonococcal urethritis, in order to investigate the activity of minocyclin in the prevention of postgonococcal urethritis.
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The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp. (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccharolytica (7 strains), Mobiluncus spp. (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp. (25 strains) and Propionibacterium spp. (7 strains). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H2, 10% CO2, 80% N2. All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates. In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp. (MIC 90 = 0.5 mg/l).
A total of 57 men and 26 women with uncomplicated gonorrhoea was treated with 1 g aztreonam intramuscularly. The cure rate was 96% and included successful treatment of 4 infections due to beta-lactamase producing organisms and 8 patients with pharyngeal involvement. The minimum inhibitory concentrations of aztreonam in vitro were lower than those of penicillin and similar to cefuroxime, and side-effects were minimal. It is concluded that aztreonam is effective against Neisseria gonorrhoeae in vivo and in vitro.
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A mechanistic understanding of ribosome function demands knowledge of the conformational changes that occur during protein synthesis. One current model proposes a conformational switch in Helix 27 (H27) of 16S rRNA involved in the decoding of mRNA. This model was based on the behavior of mutations in the 912 region of H27 of Escherichia coli 16S rRNA, which were predicted to stabilize the helix in either of two alternative conformations. This interpretation was supported by evidence from both genetics and structural biochemistry. However, recently published X-ray crystallographic structures of the Thermus thermophilus 30S subunit at different stages of tRNA selection have raised doubts regarding the validity of this model. We have therefore revisited the model genetically by constructing a H27 quadruple mutation (C912G, C910G, G885C, and G887C), which would create multiple mismatches in the proposed alternative conformation without perturbing the native H27 conformation seen in the crystal structures. Inconsistent with the H27 switch model, cells containing pure populations of quadruple mutant ribosomes grow at essentially wild-type rates. The mutants used to construct the H27 switch model all carried A2058G in 23S rRNA and C1192U in 16S rRNA as selectable markers. The quadruple mutant carrying these additional marker mutations is deleterious, and we conclude that they have a synergistic effect when combined with other mutations and are not phenotypically silent. Their presence confounded the interpretation of the original mutant phenotypes and, in light of the viability of the quadruple mutant, we conclude that the genetic evidence no longer supports the model.
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Effective therapy of gonorrhoea has changed drastically over the years, reflecting the progessive acquisition of relative antibiotic resistance by the causative organism. Although in the US. th 1974 USPHS recommendations are the best guidelines for management at present, recent epidemiological trends may obviate some of these provisions. The most important of these trends is the emergence of R-factor carrying strains capable of producing penicillinase, thereby making these strains absolutely resistant to clinically achievable levels of penicillin. This review analyses this problem in the context of reasonable therapeutic goals and also discusses optimum management of patients with such complications as pharyngeal infection, pelvic inflammatory disease and disseminated gonococcal infection.
1. The pharmacokinetics and fate of 3H-trospectomycin sulphate, a novel aminocyclitol antibiotic, were examined in male and female rats after intramuscular (i.m.), intravenous (i.v.) and subcutaneous (s.c.) dosing. 2. Total radioactivity levels in plasma were associated with unchanged trospectomycin. Two radioactive components were found in urine, one was indistinguishable from trospectomycin and the other was probably a degradation product formed after excretion or during storage rather than a metabolite. 3. The disappearance of drug from plasma followed a biphasic pattern with half lives of 0.3-0.4 h and 45-80 h and a large distribution volume, which indicated some retention of drug by tissues. Clearance rates were within the normal range for glomerular filtration rate, which indicated that the primary process of elimination is filtration of unchanged drug. 4. Excretion was initially rapid (greater than 40% by 4 h) and mainly into urine (faecal excretion greater than 20%). Urinary excretion was significantly larger in males than females but faecal excretion was significantly smaller, so that there was no significant difference in total excretion. 5. The bioavailability following s.c. dosing was only approximately 75% but there were few other biologically significant differences between the routes of administration. Absorption following i.m. and s.c. dosing was rapid. 6. Clearance rate and volume of distribution were higher in males than females. Over the dose range 50-200 mg/kg the pharmacokinetics appeared to be mostly linear.
Consecutively isolated gonococcal strains from 10 representative geographical areas in Sweden were serogrouped according to the previously described W antigen class. The majority of the strains were antibiotic susceptibility tested and approximately one fourth of them were auxotyped. Statistically significant differences of the serogroup patterns were demonstrated between the 2 largest towns, which represented highly urbanized areas where serogroup W II dominated, and the middle sized towns with adjoining rural districts, where serogroup W I dominated. The serogroup patterns of the strains isolated in 3 university towns were representative for Sweden as a whole. Statistically significant differences were demonstrated between urban and rural areas with regard to the susceptibility of gonococci to beta-lactam antibiotics. About 95% of serogroup W I strains were highly sensitive to ampicillin whereas about 65% and 90% of W II and W III strains, respectively, showed decreased susceptibility. The majority of the auxotyped strains belonged to 4 main types: Pro-, Pro-Arg-Ura-, AHU- and prototrophic. The majority of the AHU- strains belonged to serogroup W I and were highly susceptible to beta-lactam antibiotics and tetracycline. Many of the Pro-Arg-Ura-strains belonged to 2 particular subserogroups within serogroup W II and showed increased resistance to beta-lactam antibiotics. Serological classification of gonococci by co-agglutination is a simple and rapid technique without need of special equipment. It could serve 2 purposes: 1) as a confirmation test for gonococci cultured from clinical specimens; 2) for serogrouping of gonococcal isolates to study the epidemiology of gonorrhoea with regard to geographical areas, race, sexual preference, treatment failure and other demographic and medical factors.
Minocin at 500 micrograms/ml of semen extender eliminated ureaplasma from naturally or artificially infected bovine semen. Minocin with lincospectin eliminated Acholeplasma laidlawii, Mycoplasma bovigenitalium, bovis, canadense, and arginini from artificially infected semen. Stabilization times of 15 min at 35 C and 3 h at 4 C are important considerations to maximize antibiotic activity.
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